The overall objective of this study is to determine whether various anticancer drugs can effect sialoprotein synthesis and whether surface glycoproteins can influence the uptake and cytolytic activity of these drugs by human neoplastic cells in vitro. An in vitro model system involving a cultured lymphoblastoid cell line will be used to quantitate sialoprotein synthesis. In this system, 14C-labeled substrate is incubated with the cell and the amount of labeled sialoprotein on the cell surface is quantitated by counting the radioactivity of extracted cells. This reaction, mediated by an enzyme, sialyl transferase, is located predominantly at the outer cell surface. In these studies, anticancer drugs in pharmacological dosages will be added to the incubation medium along with the labeled substrate. After incubation, the newly synthesized, labeled sialoprotein will be quantitated and compared to the controls. Drugs to be tested include many of the currently used cancer chemotherapeutic agents. The identification of drugs that could inhibit sialic acid synthesis might be potentially useful as an adjuvant in designing immunotherapy protocols. In a second group of experiments, the sugar portion of various glycoproteins will be removed from human leukemic cells by enzymatic digestion. These cells and untreated control cells will be incubated with either labeled or unlabeled anticancer drugs for various time periods. The cells incubated with labeled drugs will be extracted and radioactivity counted. These experiments will determine whether glycoproteins, especially sialic acid, can alter the uptake of certain anticancer drugs. In the group treated with unlabeled drugs, the washed cells will be incubated in new culture medium and the degree of cell death quantitated during the incubation period by the trypan blue exclusion technique. These experiments are designed to determine whether removal of sialic acid from cell surfaces can influence the susceptibility of these cells to the anticancer drugs. These studies may provide some insight into the development of resistance to anticancer drugs, which comprises a major problem in the treatment of many cancers. BIBLIOGRAPHIC REFERENCE: The Effects of Cytidine Monophosphate on the Regeneration of Sialoproteins on the Surface of Cultured Lymphoma Cells. Richard D. Maca and Adrianne Hakes. Biochem Biophys Res Commun 74:1660-1666, 1977.